Messages from a pituitary surgeon

The Japan Endocrine Society (JES) was established in 1925 by Professor Kanji Tsuji, Faculty of Medicine, Kyoto Imperial University, and since then, has played a central role in clinical and basic research on endocrine diseases in Japan. It has also made great contributions to the development of medicine in Japan and overseas, and to the maintenance and improvement of public health. I am pleased that such a prestigious academic society has entered the countdown toward the 100^th anniversary of its founding. I also feel most fortunate that I will surely be able to experience such a memorable milestone when we reach it.

Surprisingly, I received a request from Endocrine Journal Editorial Board of the JES to contribute a statement as a recipient of the 2018 Distinguished Endocrinologist Award (DEA) to the TOWARD JES 100^th ANNIVERSARY: REMARKS FROM HONORARY MEMBERS, which is a special section of Endocrine Journal dedicated to the theme. I have specifically been requested to contribute an essay that would be of interest to read and which would be a fusion of the scientific and the social, including thoughts on the 100^th anniversary of the JES and a message to junior members. However, it seems like a difficult request to me, as I have already retired and recently seem to have become somewhat forgetful. I investigated the DEA itself again and it turns out that this award was apparently inherited from the Best Endocrine Surgeon of the Year, which was started in 2004. This surgeon’s award continued for five years until 2008, but its name was changed to DEA after 2009 as there were no further suitable candidates for the surgeon’s award. During that time, 14 medical doctors, including myself, were awarded the DEA, and of the 14, 12 were endocrinologists. The remaining two were Dr. Yoshiyuki Osamura, the grand personage of the Japanese Society of Pathology who received this award in the first year (2009), and myself, a neurosurgeon. I reached the conclusion that writing down my thoughts as a pituitary surgeon while looking back on my life would be my message to the JES and junior members.

In 1977, after graduating from Akita University, I entered Toranomon Hospital as a neurosurgical intern. After completing my internship, I continued to engage in medical care, research, and education as a member of the Department of Neurosurgery at Toranomon Hospital. In the first year of training, Dr. Tadashi Aiba, who was the head of the Department at that time, asked me to conduct research on the following theme: “The significance of measuring pituitary hormones in the cerebrospinal fluid in the diagnosis of pituitary tumors.” Although I was only in my first year, I worked desperately on this theme, which became the first opportunity for me to pursue pituitary disease as my life’s work. In my daily practice, I have come to take care of many patients with pituitary disease. Meanwhile, in the Department of Endocrinology, there were leading teachers such as Drs. Yoshimasa Shishiba, Shinji Sawano, Taeko Shimizu, and Yasunori Ozawa. Their assessments of surgical results of pituitary tumors were very strict, and surgery for Cushing’s disease, in which the first surgery is extremely important, was referred to other specialized facilities at the time. This demonstrates that the best treatment choice for patients was carefully considered and that patient-centered care was the top priority. However, it was precisely because of their strict standards of judgment that I never compromised, and the idea of aiming for the best treatment results possible with surgery, which has remained unchanged to this day, has become my strong belief in dealing with functioning pituitary tumors. It is no exaggeration to say that I have been educated and brought up by the endocrinologists at Toranomon Hospital and other endocrinologists around Japan, who have referred many pituitary patients to me (Fig. 1).

Fig. 1

Department of Endocrinology and Department of Hypothalamic & Pituitary Surgery joint year-end party. In the front row are the three successive directors of the Endocrinology Department (from right to left): Drs. Yasuhiro Takeuchi, Yasunori Ozawa, and Yoshimasa Shishiba.

A few years after I became a qualified neurosurgeon, Dr. Aiba encouraged me to study pituitary pathology abroad, and I had the opportunity to study pituitary pathology under Professor Kalman T. Kovacs (Division of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada), who was the most famous endocrine pathologist at the time and had played a significant role in the development of pituitary pathology (Fig. 2). Although my experience there lasted for only a year, it was a very meaningful time as I was able to put aside clinical practice and devote myself to experimental research daily. During this period, I was also able to publish several papers in professional journals including The Journal of Clinical Endocrinology and Metabolism and Journal of Neurosurgery. In addition, I could discuss about pituitary pathology every day with Dr. Toshiaki Sano, who became a close collaborator of mine throughout my life (Fig. 2). During my stay in Toronto, I also met with Dr. Gerard Guiot and Dr. Jules Hardy, who are both legendary giants in the field of pituitary surgery, and I was able to observe transsphenoidal surgeries (TSS) performed by Dr. Hardy himself at Notre-Dame Hospital in Montreal (Fig. 3). Dr. Hardy popularized TSS worldwide as a surgical approach for pituitary tumors by applying intraoperative fluoroscopy and using an operating microscope. Therefore, TSS has also been referred to as “Hardy’s operation” in honor of his achievements. Looking back, it was indeed one of the happiest times of my life. Through this precious overseas experience, I was able to realize the alluring charm and depth of pituitary pathology, and it was a turning point that made me strongly decide to pursue clinical and basic research on pituitary tumors as my life’s work. Recently, I have heard that junior doctors tend to avoid studying abroad. However, I would like to encourage young members to consider actively studying abroad as it can be beneficial not only for their careers but also for their own lives.

Fig. 2

Professor Kalman T. Kovacs and his wife Mrs. Eva Horvath (left). Drs. Setsuyo Kawakita, Toshiaki Sano, and me (all three of us studied pituitary pathology in Toronto almost simultaneously) with Dr. Kovacs in Nagoya (right).

Fig. 3

At the left is Professor Gerard Guiot and the second from the right is Professor Jules Hardy. Operating theater at Notre-Dame Hospital in Montreal (1987).

When I returned to Japan from Toronto at the age of 38 and started working as a pituitary surgeon at Toranomon Hospital, I was most humbly moved and overjoyed when I was asked by Dr. Shishiba to perform surgery on two patients with Cushing’s disease. I clearly remember this event as if it were only yesterday.

I then begged the director of the hospital, Dr. Kinori Kosaka, to grant me a small laboratory space, after which I spent my days doing medical practice and my nights doing experiments. Simultaneously, I began to seek opportunities to present my research results at the JES and the Endocrine Society in the USA and joined as a member of both societies. In addition, with the primary goal of improving the quality of my research, I conducted joint researches with many other institutions. Because only surgeons can obtain tumor specimens, to ensure that tumor specimens can be used by many researchers in the future, DNA, RNA, and paraffin blocks are preserved in all cases, where patient consent is obtained.

Since then, with the cooperation of the Department of Endocrinology and Pediatric Endocrinology at Toranomon Hospital, we have sought to provide the best and most suitable medical care for patients with hypothalamic and pituitary diseases across all age groups. Furthermore, with the understanding and cooperation of endocrinologists throughout Japan, the number of referred patients has steadily increased. In April 2005, we established the first Department of Hypothalamic and Pituitary Surgery in Japan at Toranomon Hospital as a separate facility from the Department of Neurosurgery. By becoming an independent department, it made it possible to better provide patients with more specialized up-to-date medical care in a multidisciplinary manner. Pituitary tumors and other parasellar lesions are commonly accompanied by endocrine disorders due to pituitary hormone hypersecretion from the tumor itself or hormone impairment by the tumor. Lesions such as these require long-term multidisciplinary treatment. Therefore, specialized knowledge and experience are required to correctly diagnose and effectively treat these diseases. I am proud that this concept was the forerunner of the Pituitary Center of Excellence (PCOE) idea, later claimed in the USA (Neurosurgery 2012; 71: 916–926). Simultaneously, in 2005, in cooperation with Dr. Akira Shimazu, we established the Pituitary Disease Patients Association (Kasuikai in Japanese) to provide more accurate information to patients with intractable lifelong hypothalamic pituitary diseases. Since then, Kasuikai has been managed by the patients themselves, and this unique patient association has developed well up to this day (Fig. 4). It functions not only as a place for the exchange of valuable information among patients, but also as a major driving force in the field, such as when it led to seven pituitary diseases to be newly recognized as specific diseases in October 2008.

Fig. 4

Lecture by Dr. Akira Shimazu at the Kasuikai in July 2014 (left). Drs. Michio Otsuki, Wataru Kameda, and Hidenori Fukuoka (standing, from left to right) with staffs (in the front row) of the Kasuikai booth in the Annual Congress of JES (right).

Since Dr. Kenichi Oyama and I started the Department of Hypothalamic and Pituitary Surgery at Toranomon Hospital in 2005, Drs. Hiroshi Nishioka, Noriaki Fukuhara, Kentaro Horiguchi, and Okada [Mitsuo Yamaguchi-Okada] joined us until I retired in March 2018 (Fig. 1). Other pituitary surgeons interested in pituitary surgery have also visited and joined us not only from Japan but also from many other Asian countries. Since the founding of this unique center, we have continued to strive to make it an excellent PCOE in Japan.

To be recognized as a PCOE, the following three primary missions are proposed: 1) providing optimal multidisciplinary clinical care to patients with pituitary tumors and related disorders; 2) providing residency, fellowship training, and/or continuing medical education and patient support; and 3) contributing to research in the field of pituitary disorders. The first mission is the most important point that all doctors in our department have put the most effort into, and I have aimed to introduce and popularize several new surgical techniques. These surgical method improvements are the result of challenging conventional practices tempered by the bitter experience of failure. I hope that junior members form the habit of asking themselves whether what they have been taught as immutable laws by their seniors and/or textbooks are indeed true or not. In our field, the cavernous sinus has long been believed to be a “no man’s land,” and, therefore, senior doctors have strictly instructed their juniors not to tamper with this area. In response to this, a great deal of ingenuity and creativity has been put into it, and it is now no longer the intractable “no man’s land” it once was. This indicates that properly educated doctors can now tackle this area. At the same time, cavernous sinus tumor invasion remains the most unfavorable preoperative factor affecting surgical outcome, and I have always thought that surgical outcome for functional pituitary tumors would be greatly improved if the tumor invading the cavernous sinus could be appropriately approached and removed. In 2004, when I first reported the resection method for invasive cavernous sinus tumors, it was ridiculed as an extremely dangerous and barbaric procedure. Recently, however, tumors invading the cavernous sinus have also become targets of surgical resection in some institutions. In addition, for large invasive pituitary tumors, I first applied a simultaneous combined transcranial and transnasal approach in Japan. Again, this was also a last-ditch measure conceived from bitter experiences in the past; we have often experienced cases of critical or fatal intratumoral hemorrhage from residual tumors. When I first announced this intriguing surgical approach in a meeting in Japan in 2008, I received harsh criticisms that such a complicated invasive procedure should not be performed. However, with the widespread use of endoscopy in pituitary surgery, this combined surgery is becoming more common, even in Japan, for the surgical treatment of giant invasive pituitary tumors, which are difficult to remove using either the transnasal or transcranial approach alone (Fig. 5). In this way, I have made every effort to establish a surgical technique that enables safe and maximum resection of tumors of any size. As a result of these efforts, I was honored with a prestigious DEA in 2018. Under such circumstances, the number of operations per year was approximately 350, which may be one of the largest in the world. At the same time, the number of patients referred for re-operation from other hospitals accounts for 10% to 20%, indicating that our institute has been considered the last bastion for many patients with complicated pituitary tumors (Fig. 6). However, to provide multidisciplinary and personalized medicine to these patients, a collaborative system of endocrinologists, pediatricians, neurosurgeons, cerebrovascular surgeons, pathologists, otolaryngologists, ophthalmologists, and radiologists is essential. Young members should always consider the importance of the second mission; they should recognize the importance of building good relationships with doctors in other related departments on a daily basis and maintaining constant communication with them. In addition to educating trainees and residents of Toranomon Hospital, we have actively allowed qualified visitors to see operations and commissioned trainees throughout Japan. Furthermore, we regularly held pituitary case conferences with neurosurgeons and endocrinologists working in the Kanto area to improve mutual knowledge by discussing problematic but interesting cases.

Fig. 5

Simultaneous combined transcranial and transnasal approach (A, B, C). Initially, it was performed with two operating microscopes (A). Recently, the microscope has been replaced by an endoscope in the transnasal approach (C). Pre- and postoperative magnetic resonance imaging of a large nonfunctioning pituitary adenoma (D-1, 2). The tumor was almost completely removed using the combined method (D-2).

Fig. 6

This graph presents the details of the 5,093 pituitary and parasellar tumors experienced from 2005 to the end of 2021.

We also hold a pituitary educational seminar yearly for young neurosurgeons and endocrinologists who are responsible for the next generation. In this seminar, educational lectures, mainly for the treatment of pituitary diseases, are provided on the first day, and a cadaver dissection course is held on the second day with the understanding and cooperation of the Department of Anatomy, Tokyo Medical University, using a donated body to help participants better understand the surgical anatomy for transnasal approaches (Fig. 7). Such conferences and seminars are still being conducted and further developed by Dr. Nishioka and our colleagues, who succeeded me.

Fig. 7

The 2^nd Pituitary Seminar (2015). Group photograph at the hands-on seminar in the autopsy room of Tokyo Medical University on the second day.

Until 2018 when I retired, in cooperation with Professor Sun Ho Kim (Department of Neurosurgery, Yonsei Brain Research Institute, Yonsei University College of Medicine), we held an annual educational lecture and cadaver dissection course at Yonsei University in South Korea, mainly for young neurosurgeons from developing countries in Asia (Fig. 8). They were all eager to improve their knowledge of pituitary diseases and surgical skills in transnasal approaches. In 2011, we started the Pituitary Expert Meeting in Asia with Dr. Hideki Katakami, Dr. Shimazu, and Dr. Seong Yeon Kim (Department of Internal Medicine, Seoul National University College of Medicine) for the purpose of understanding the situation in each country, improving the level of medical care for pituitary diseases, and deepening exchanges between doctors specializing in pituitary diseases in major Asian countries. We have since held annual academic conferences in Japan, Korea, and China (Fig. 9). I hope that young members who are responsible for the training and education of the next generation should have a wider perspective, focusing not only on the skills they have acquired, but also on improving the overall level of medical care, while educating and disseminating useful and correct information to patients.

Fig. 8

The 3^rd Asian-Pacific Transsphenoidal Approach and Neuroendoscopy Workshop (Seoul, 2016). Group photograph (left) and the lecture of anatomy in cadaver dissection course (right). Professor Sun Ho Kim is seated, the fifth from the left in the front row.

Fig. 9

The 6^th Pituitary Expert Meeting in Asia (2017). Core members from Japan and South Korea. Professor Seong Yeon Kim is in the front row on the left (left). Group photograph of all the participants. Front row, 5^th from right was the invited guest speaker Ken K. Y. Ho (Garvan Institute of Medical Research, Sydney, Australia) (right).

Regarding the third mission of contributing to research in the field of pituitary disorders, we have conducted research with many doctors from related departments and presented the results obtained at academic conferences and published papers in English. However, because of the nature of the work in the clinical hospital, we could not conduct basic research alone, so we have collaborated with domestic and overseas research institutes regarding various basic research issues. Writing and publishing papers in English is important for publicly disseminating to the world the results you obtained from your clinical research and/or interesting cases. At the same time, writing a paper is not only important for fostering the capacity for scientific and rational thought, but also the act of logically compiling and completing a thesis that leads to the improvement of one’s own medical level for clinicians. Therefore, I hope that all young members will endeavor to publish many such scientific papers throughout their lives.

With many colleagues, I have always sought to implement the abovementioned three missions, and have made every effort to establish a PCOE that is as close to the ideal as possible. Not only surgical skills but also knowledge of endocrinology is important for pituitary surgeons to provide better medical care to patients, and I have constantly sought to deepen exchanges with many endocrinologists over the years through the JES and the Japanese Society for Hypothalamic and Pituitary Tumors. However, many endocrinologists have mentioned the difficulty of collaborating with neurosurgeons. Thus, I am grateful for the understanding and efforts of President Hiroshi Ito and Director Masanobu Yamada (Chairperson of the Board Certification Committee), a new board-certified endocrinologist (neurosurgery) in the JES in 2018. As of 2022, the JES comprises 21 certified endocrine educators, 166 board-certified endocrinologists, and 12 certified educational institutes in the field of neurosurgery; further development is expected in the future. In the past, Professor Naoki Kageyama (Department of Neurosurgery, Nagoya University Graduate School of Medicine) and Professor Akira Teramoto (Department of Neurosurgery, Nippon Medical School) served as the chairmen of the 58^th and 83^rd Annual Congresses of JES, respectively. Through this system, I strongly believe that neurosurgeons can expect to improve their knowledge of matters related to endocrinology and metabolism, and more importantly, that endocrinologists and neurosurgeons can deepen their exchanges, share their abundant knowledge and skills, and mutually enhance one another. Today, when multidisciplinary and personalized medicine is highly recommended, pituitary neurosurgeons must deepen exchanges with members of the JES and share their knowledge and skills to provide better medical care to patients with pituitary diseases. I am convinced that this will prove extremely useful and important for patients as well.

As the JES prepares to celebrate its upcoming 100^th anniversary, as a member of the Society, I strongly desire for it to continue the good traditions of the past while boldly tackling new challenges and embarking on another 100-year journey.

Biographies

Shozo Yamada

Honorary Member

Director, Hypothalamic and Pituitary Center, Moriyama Neurological Center Hospital

E-mail: [e-mail]

Careers in JES

2022– Honorary Member

2019– Senior Councilor

2017–2019 Director (General Affairs)

2015–2017 Director (Finance)

2007– Councilor

1986– Member

JES Awards

2018 Distinguished Endocrinologist Award